April 20, 2020
Fremont, Calif.—Verseon, a technology-based pharmaceutical company employing a computer-driven platform to develop a diverse drug pipeline, published preclinical findings on its precision oral anticoagulant (PROAC) clinical development candidate VE-1902 in the peer-reviewed journal Thrombosis Research. The paper is entitled “VE-1902—A direct thrombin inhibitor with reversible covalent mechanism of action shows efficacy with reduced bleeding in rodent models of thrombosis” (https://doi.org/10.1016/j.thromres.2020.04.020).
VE-1902, which is currently in a Phase I clinical trial, belongs to the new class of anticoagulants developed Verseon called PROACs that demonstrate a unique combination of efficacy with lower bleeding in preclinical testing. This newly published data suggests that PROACs could be expected to address a significant need for a safe anticoagulant suitable for prolonged combination therapy with antiplatelet drugs. Millions of patients worldwide could benefit from safe long-term co-dosing of an anticoagulant with one or more antiplatelet drugs (e.g.: PlavixTM, aspirin) to prevent strokes or heart attacks. However, current NOACs (novel oral anticoagulants) are not suitable for such therapy because they greatly increase patients’ risk of uncontrolled bleeding.
In multiple preclinical studies, Verseon demonstrated that PROACs like VE-1902 prevent the formation of blood clots but do not disrupt platelet function. Preservation of platelet function provides a biological explanation for the significantly reduced bleeding of PROACs compared to NOACs. In addition, this characteristic enables PROACs to influence the coagulation cascade more precisely, making them more suitable for co-administration with antiplatelet drugs.
“Acceptance of the VE-1902 findings in a respected peer-reviewed journal is further validation of the importance and novelty of the class of anticoagulants we are developing” said Dr. David Kita, Vice President of R&D at Verseon.
The following is an abstract of an article published in Thrombosis Research on April 19, 2020. To read the full article, click here.
ABSTRACT: VE-1902-A direct thrombin inhibitor with reversible covalent mechanism of action shows efficacy with reduced bleeding in rodent models of thrombosis
Thrombosis Research 2020 April 19, 190: 112-121
INTRODUCTION: High incidence of bleeding events remains a key risk for patients taking anticoagulants, especially those in need of long-term combination therapy with antiplatelet agents. As a consequence, patients may not receive clinically indicated combination antithrombotic therapy. Here, we report on VE-1902, a member of a novel class of precision oral anticoagulants (PROACs) that combines effective anticoagulation with reduced bleeding in preclinical testing.
METHODS AND RESULTS: Acting through covalent, reversible active-site modification of thrombin similar to a previously described molecule, VE-1902 shows potency and selectivity for thrombin inhibition in human plasma comparable to clinically relevant direct thrombin inhibitors (DTI) such as argatroban and dabigatran (thrombin generation assay ETP EC50 = 1.3 μM compared to 0.36 μM and 0.31 μM for argatroban and dabigatran; >100-fold selectivity against related serine proteases). Unlike the current anticoagulants, VE-1902 does not significantly inhibit thrombin-mediated platelet activation in in vivo models of thrombosis. In the thrombin generation assay, the compound inhibits thrombin formation without significantly delaying the initiation phase of the clotting cascade. These features are possibly responsible for the observed reduced bleeding in tail bleeding and saphenous vein bleeding models. Consistent with this novel pharmacological profile, VE-1902 shows efficacious anticoagulation in several fibrin-driven animal models of thrombosis (arteriovenous shunt, venous stasis thrombosis, and thrombin-induced thromboembolism models), whereas it does not significantly prevent arterial occlusion in the platelet dependent FeCl3 model.
CONCLUSIONS: By leaving platelet activation following vascular injury mostly unaffected, VE-1902, and the PROACs more generally, represent a new generation of precision anticoagulants with reduced bleeding risk.
About Verseon’s anticoagulation program
Verseon’s precision oral anticoagulants (PROACs) are potent, highly selective, reversible covalent inhibitors of thrombin. PROACs have shown excellent efficacy in multiple preclinical studies. The fact that PROACs do not disrupt platelet function could explain the low bleeding risk of these drug candidates and makes them excellent candidates for use in long-term combination anticoagulant-antiplatelet therapy. The first development candidate, VE-1902, is currently in clinical trials. In addition to other unique properties of PROACs, VE-1902 has very low renal clearance, a highly desirable feature for patients with impaired kidney function. In its anticoagulation program, Verseon also has a second development candidate, VE-2851, which is expected to enter clinical trials at a later date.
Verseon Corporation (www.verseon.com) is developing disruptive life-science technology to advance global health. The clinical-stage company is using its proprietary, computational drug discovery platform to discover new drug candidates that are unlikely to be found using conventional methods. Pairing its computational platform with a comprehensive in-house chemistry and biology workflow, the company has built a growing pipeline of drug programs. Verseon currently has drug programs in the areas of anticoagulation, diabetic retinopathy, hereditary angioedema, and oncology.